DESCRIPTION: (Applicant's Abstract) The long-term objective is to prepare a potent, selective inhibitor of cocaine binding at the dopamine transporter that has a minimal effect on the reuptake of dopamine. Inhibition of this binding could result in a drug useful in blunting the craving for cocaine, a substance that has severe abuse problems in a wide spectrum of the United States population. This objective will be approached by a systematic structural modification using molecular modeling techniques, of the clinically used mazindol, a known inhibitor of the cocaine binding site with a poor dopamine uptake/cocaine binding ratio (1.04). A second objective is to correlate, if possible, the structure-activity relationships (SAR) of the mazindol analogs with R-cocaine and other dopamine transporter inhibitors with the aim of designing novel inhibitors of the cocaine receptor.